HLM006474 inhibits cell survival and synergizes with HDACi and Pi in vitro and vivo as well as patient-derived CTCL cells. (A) Protein levels of PEG10 and KLF2 in HH cells treated with increasing concentration of HLM006474 for 72 hours. (B) Specific apoptosis of PEG10-suppressed (shPEG10) and control (Ctrl) HH cells under exposure to different-dose HLM006474 for 48 hours. (C) Macroscopic pictures of xenograft tumors after subcutaneously injecting HH cells. Tumor-bearing animals were randomized into 2 groups (n = 4, each) and intraperitoneally injected with either 20% captisol as vehicle control or 30 mg/kg HLM006474 3 times a week for 2 weeks. (D,E) Median tumor volume (D) and body weights (E) in control and treated xenograft mice were measured over treatment times. (F) Specific apoptosis of PBMCs from 2 leukemic CTCL patients (L-CTCL) and healthy donors (Normal) under exposure to increasing concentration of HLM006474 for 24 hours. PEG10 mRNA expression levels (TPM) are shown on the right panel. (G,H) Specific apoptosis and combination index for the combination of HLM006474 (HLM) with SAHA (G) and with bortezomib (BZ) (H) in HH cells. (I,J) Specific apoptosis and combination index for the combination of HLM006474 (HLM) with SAHA (I) and with bortezomib (BZ) (J) in PBMCs from L-CTCL patients. Data are represented as the mean standard deviation. *P < .05; **P < .01. ns, no significance; CI, combination index; Fa, fraction affected.